Self-assembling chimeric protein for the construction of biodegradable hydrogels capable of interaction with integrins expressed on neural stem/progenitor cells.
Self-assembling chimeric protein for the construction of biodegradable hydrogels capable of interaction with integrins expressed on neural stem/progenitor cells.
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DOI：
10.1021/bm701423d
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发表时间：
2008-04
影响因子：
6.2
通讯作者：
T. Nakaji-Hirabayashi;Koichi Kato;H. Iwata
中科院分区：
文献类型：
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作者：
T. Nakaji-Hirabayashi;Koichi Kato;H. Iwata
神经干细胞/祖细胞移植到大脑后存活率低是限制帕金森病细胞治疗效果的主要问题。为了克服这个问题，我们正在设计基于角蛋白的水凝胶，作为防止炎症细胞浸润的物理屏障。水凝胶的另一个特点是含有促进整合素介导的细胞粘附的多肽。为了构建这种水凝胶，通过重组DNA技术合成了由层粘连蛋白衍生的α -螺旋多肽和球状结构域组成的嵌合蛋白，并与提取的角蛋白共同组装，通过α -螺旋片段的分子间卷曲结合形成水凝胶。发现神经球形成细胞特异性粘附在角蛋白基复合水凝胶上，增殖活跃，存活率高。这些结果表明，复合水凝胶为神经祖细胞的存活和增殖提供了适宜的微环境。
The poor survival of neural stem/progenitor cells following transplantation into the brain is the major problem limiting the effect of cell-based therapy for Parkinson's disease. To overcome this problem, we are involved in designing keratin-based hydrogels that serve as physical barriers to prevent the infiltration of inflammatory cells. Another feature of the hydrogels is to contain a polypeptide that promotes integrin-mediated cell adhesion. To construct such hydrogels, a chimeric protein consisting of an alpha-helical polypeptide and a globular domain derived from laminin was synthesized by means of recombinant DNA technology and coassembled with extracted keratins that form hydrogels through intermolecular coiled-coil association of alpha-helical segments. It was found that neurosphere-forming cells specifically adhered to the keratin-based composite hydrogel and actively proliferated at a high survival rate. These results suggested that the composite hydrogel provides microenvironments suitable for the survival and proliferation of neural progenitor cells.